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Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity

Protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. Intracellular Plasmodium parasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class I (MHC-I) molecules on infected cells, yet they actively remodel their h...

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Autores principales: Montagna, Georgina N., Beigier-Bompadre, Macarena, Becker, Martina, Kroczek, Richard A., Kaufmann, Stefan H. E., Matuschewski, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128355/
https://www.ncbi.nlm.nih.gov/pubmed/25073641
http://dx.doi.org/10.1128/mBio.01321-14
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author Montagna, Georgina N.
Beigier-Bompadre, Macarena
Becker, Martina
Kroczek, Richard A.
Kaufmann, Stefan H. E.
Matuschewski, Kai
author_facet Montagna, Georgina N.
Beigier-Bompadre, Macarena
Becker, Martina
Kroczek, Richard A.
Kaufmann, Stefan H. E.
Matuschewski, Kai
author_sort Montagna, Georgina N.
collection PubMed
description Protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. Intracellular Plasmodium parasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class I (MHC-I) molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. Whether exported liver-stage proteins constitute better candidates for MHC-I antigen presentation to CD8(+) T lymphocytes remains unknown. Here, we systematically characterized the contribution of protein export to the magnitude of antigen-specific T-cell responses against Plasmodium berghei liver-stage parasites in C57BL/6 mice. We generated transgenic sporozoites that secrete a truncated ovalbumin (OVA) surrogate antigen only in the presence of an amino-terminal protein export element. Immunization with live attenuated transgenic sporozoites revealed that antigen export was not critical for CD8(+) T-cell priming but enhanced CD8(+) T-cell proliferation in the liver. Upon transfer of antigen-specific CD8(+) T cells, liver-stage parasites secreting the target protein were eliminated more efficiently. We conclude that Plasmodium parasites strictly control protein export during liver infection to minimize immune recognition. Strategies that enhance the discharge of parasite proteins into infected hepatocytes could improve the efficacy of candidate preerythrocytic malaria vaccines.
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spelling pubmed-41283552014-08-12 Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity Montagna, Georgina N. Beigier-Bompadre, Macarena Becker, Martina Kroczek, Richard A. Kaufmann, Stefan H. E. Matuschewski, Kai mBio Research Article Protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. Intracellular Plasmodium parasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class I (MHC-I) molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. Whether exported liver-stage proteins constitute better candidates for MHC-I antigen presentation to CD8(+) T lymphocytes remains unknown. Here, we systematically characterized the contribution of protein export to the magnitude of antigen-specific T-cell responses against Plasmodium berghei liver-stage parasites in C57BL/6 mice. We generated transgenic sporozoites that secrete a truncated ovalbumin (OVA) surrogate antigen only in the presence of an amino-terminal protein export element. Immunization with live attenuated transgenic sporozoites revealed that antigen export was not critical for CD8(+) T-cell priming but enhanced CD8(+) T-cell proliferation in the liver. Upon transfer of antigen-specific CD8(+) T cells, liver-stage parasites secreting the target protein were eliminated more efficiently. We conclude that Plasmodium parasites strictly control protein export during liver infection to minimize immune recognition. Strategies that enhance the discharge of parasite proteins into infected hepatocytes could improve the efficacy of candidate preerythrocytic malaria vaccines. American Society of Microbiology 2014-07-29 /pmc/articles/PMC4128355/ /pubmed/25073641 http://dx.doi.org/10.1128/mBio.01321-14 Text en Copyright © 2014 Montagna et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Montagna, Georgina N.
Beigier-Bompadre, Macarena
Becker, Martina
Kroczek, Richard A.
Kaufmann, Stefan H. E.
Matuschewski, Kai
Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity
title Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity
title_full Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity
title_fullStr Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity
title_full_unstemmed Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity
title_short Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity
title_sort antigen export during liver infection of the malaria parasite augments protective immunity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128355/
https://www.ncbi.nlm.nih.gov/pubmed/25073641
http://dx.doi.org/10.1128/mBio.01321-14
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